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Anaphylactic events triggered by mRNA COVID-19 vaccines are neither serious nor frequent. Kounis syndrome is described as the concomitant occurrence of acute coronary events and hypersensitivity reactions induced by vasospastic mediators after an allergic event. Kounis syndrome caused by vaccines is very rare. Up to now, only a few cases of allergic myocardial infarction after mRNA COVID-19 vaccine administration have been reported. Takotsubo cardiomyopathy is a syndrome characterized by transient wall movement abnormalities of the left ventricular apex, mid-ventricle, or other myocardial distribution, usually triggered by intense emotional or physical stress. Takotsubo cardiomyopathy after COVID-19 vaccine administration has been reported, usually with a delayed onset. A new entity characterized by the association of adrenaline administration, Takotsubo cardiomyopathy, anaphylaxis, and Kounis hypersensitivity was recently described: the ATAK complex. Here, we report a case of Takotsubo cardiomyopathy that occurred together with an anaphylactic reaction to an mRNA COVID-19 vaccine that required the use of adrenaline. The timing of the allergic reaction and the referenced clinical symptoms could not exclude the idea that Kounis syndrome occurred. Therefore, we can assume the patient presented the ATAK complex. We believe that highlighting on this ATAK complex will aid the application of proper diagnostic, preventive and therapeutic measures.

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Background and Objectives: Bones and the skeletal muscle play a key role in human physiology as regulators of metabolism in the whole organism. Bone tissue is identified as a complex and dynamic living unit that could react to physical activity. Hormones, growth factors, signaling factors, and environmental factors control osteogenesis, and it could be regulated at a post-transcriptional level. MicroRNAs (miRNAs) can interfere with mRNAs translation. Increasing data suggest that miRNAs, through different pathways, are involved in the regulation of bone marrow mesenchymal stem cells (BMSCs) differentiation and physical activity-induced bone remodeling. The purpose of this narrative review is to investigate the potential protective role played by physical activity in affecting miRNAs expression in close tissues and elaborate on the complex network of interplay that could drive various metabolic responses of the bone to physical activity. Materials and Methods: A bibliographic search of the scientific literature was carried out in scientific databases to investigate the possible effect of physical activity on age-related features detected in the musculoskeletal system. Results: Several studies suggested that the musculoskeletal system interacting at a biomolecular level could establish crosstalk between bone and muscle in an endocrine or paracrine way through myokines released by muscle at the periosteal interface or in the bloodstream, such as irisin. Mechanical stimuli have a key role in bone formation and resorption, increasing osteogenesis and downregulating adipogenesis of BMSC via regulation of expression of runt-related transcription factor 2 (Runx2) and peroxisome proliferator-activated receptor gamma (PPARγ), respectively. Conclusions: Increasing data suggest that miRNAs, through different pathways, are involved in the regulation of BMSCs differentiation and physical activity-induced bone remodeling. Modulation of miRNAs following physical exercise represents an interesting field of investigation since these non-coding RNAs may be considered defenders against degenerative diseases and as well as useful prognostic markers in skeletal and muscle-skeletal diseases, such as osteoporosis.

Background and aims: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Pancreatic cancer is one of the most aggressive cancers with a very poor 5-year survival rate and reduced therapeutic options when diagnosed in an advanced stage. The dismal prognosis of pancreatic cancer has guided significant efforts to discover novel biomarkers in order to anticipate diagnosis, increasing the population of patients who can benefit from curative surgical treatment. CA 19-9 is the reference biomarker that supports the diagnosis and guides the response to treatments. However, it has significant limitations, a low specificity, and is inefficient as a screening tool. Several potential biomarkers have been discovered in the serum, urine, feces, and pancreatic juice of patients. However, most of this evidence needs further validation in larger cohorts. The advent of advanced omics sciences and liquid biopsy techniques has further enhanced this field of research. The aim of this review is to analyze the historical evolution of the research on novel biomarkers for the early diagnosis of pancreatic cancer, focusing on the current evidence for the most promising biomarkers from different body fluids and the novel trends in research, such as omics sciences and liquid biopsy, in order to favor the application of modern personalized medicine.

Tongue motor function is crucial in a wide range of basic activities and its impairment affects quality of life. The electrophysiological assessment of the tongue relies primarily on needle electromyography, which is limited by its invasiveness and inability to capture the concurrent activity of the different tongue muscles. This work aimed at developing an intraoral grid for high-density surface electromyography (HDsEMG) to non-invasively map the electrical excitation of tongue muscles. We developed a grid of $4\times 8$ electrodes deposited over an adhesive 8- $\mu $ m thick polyurethane membrane. The testing protocol was conducted on 7 healthy participants and included functional tasks (vowels articulation and tongue movements) aimed at activating different regions of the tongue. The electrical stability of contact was assessed by measuring electrode-tongue impedances before and after the tasks. The spatial amplitude distribution of global EMG and single motor unit action potentials (MUAPs) was characterized. Electrode-tongue impedance magnitude showed no significant changes in the pre-post comparison ( $58\pm 46$ k $\Omega $ vs. $67\pm 58$ k $\Omega $ at 50Hz). Contact stability was confirmed by the quality of the signals that allowed to quantify spatiotemporal characteristics of muscle activation during the different tasks. The analysis of the spatial distribution of individual MUAPs amplitude showed that they were confined to relatively small areas on the tongue surface (range: 0.5cm2 –3.9cm $^{{2}}\text {)}$ . A variety of different spatiotemporal MUAP patterns, likely due to the presence of different muscle compartments with different fiber orientations, were observed. Our results demonstrate that the developed electrode grid enables HDsEMG acquisition from the tongue during functional tasks, thus opening new possibilities in tongue muscle assessment both at global and single motor unit level.

The intricate network of the pancreatic nervous system plays a fundamental role in physiologic functions of the endocrine and exocrine pancreas. Several pancreatic diseases affect the normal functionality of the pancreatic nervous system. This chronic derangement leads to anatomical alterations, such as neural hypertrophy and increased nerve density. Perineural invasion is a prominent feature of pancreatic cancer, contributing to cancer progression and metastasis. Despite the fact that these pathogenic mechanisms are still incompletely studied and understood, the constant occurrence of these alterations highlights their importance in the pathophysiology of the pancreatic diseases. The occurrence of anatomical changes is strictly linked to the appearance of pain. Pancreatic pain has peculiar features, and its management is complex in clinical practice. In the present review, the evidence on lifestyle, pharmacological and interventional approaches for the management of pancreatic pain is presented. Analgesic therapy is the cornerstone of pain treatment. However, it is important to identify the individual characteristic of the patients and personalize the approach to pain management. Nevertheless, the incomplete efficacy of these strategies makes this field an area of unmet needs. The study of neuroplasticity is crucial to understand the mechanisms that regulate the pathophysiology of pancreatic diseases. Several trials testing new drugs with specific neuromodulatory effects are ongoing. However, further studies are needed to investigate crucial targets to develop novel therapies for the modulation of the nervous system and the prevention of complications of pancreatic diseases. This comprehensive review summarizes the importance of the nervous system in pancreatic diseases with a special focus on its anatomy and physiology, its pathophysiological features and clinical relevance in pancreatic disease, the treatment of pancreatic pain, and the identification of future trends of research.

The present paper, in the framework of a search for a computer-aided method to detect depression, deals with experimental data of various types, with their correlation, and with the way relevant information about depression delivered by different sets of data can be fused to build a unique body of knowledge about individuals’ mental states facilitating the diagnosis and its accuracy. To this aim, it suggests the use of a recently introduced «limiting form» of the kinetic-theoretic language, at present widely used to describe complex systems of objects of the most diverse nature. In this connection, the paper mainly aims to show how a wide range of experimental procedures can be described as examples of this «limiting case» and possibly rendered by this description more effective as methods of prediction from experience. In particular, the paper contains a simple, preliminary application of the method to the detection of depression, to show how the consideration of statistical parameters connected with the analysis of speech can modify, at least in a stochastic sense, each diagnosis of depression delivered by the Beck Depression Inventory (BDI-II).

The gut microbiota is a pivotal actor in the maintenance of the balance in the complex interconnections of hepato-biliary-pancreatic system. It has both metabolic and immunologic functions, with an influence on the homeostasis of the whole organism and on the pathogenesis of a wide range of diseases, from non-neoplastic ones to tumorigenesis. The continuous bidirectional metabolic communication between gut and hepato-pancreatic district, through bile ducts and portal vein, leads to a continuous interaction with translocated bacteria and their products. Chronic liver disease and pancreatic disorders can lead to reduced intestinal motility, decreased bile acid synthesis and intestinal immune dysfunction, determining a compositional and functional imbalance in gut microbiota (dysbiosis), with potentially harmful consequences on the host’s health. The modulation of the gut microbiota by antibiotics represents a pioneering challenge with striking future therapeutic opportunities, even in non-infectious diseases. In this setting, antibiotics are aimed at harmonizing gut microbial function and, sometimes, composition. A more targeted and specific approach should be the goal to pursue in the future, tailoring the treatment according to the type of microbiota modulation to be achieved and using combined strategies.